BINDING OF HUMAN NATURAL ANTIBODIES TO NON??Gal XENOANTIGENS ON PORCINE ERYTHROCYTES1

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Abstract
Xenotransplantation is considered one of possible solutions for the serious shortage of organs and cells in transplantation. Although the alphaGal epitope (Gal alpha1,3Gal beta1,4GlcNAc-R) has been identified as being a major xenoantigen responsible for hyperacute rejection, the removal of anti-alphaGal antibody alone from human serum is insufficient to circumvent antibody-mediated immune responses. We report here the characterization of xenoreactive human natural antibodies against antigens without the alphaGal epitope (nonalphaGal xenoantigens) on porcine erythrocytes using flow cytometry and the evidence for their involvement in complement-mediated hemolysis. Furthermore, a novel protein of 45-kDa has been isolated from the porcine erythrocyte membrane as a major protein antigen recognized by human anti-nonalphaGal. The data presented here will add to our knowledge of xenoantigens on porcine red cells and be important for developing strategies to produce modified red cells immunologically compatible to humans.